We investigated whether autoimmune cholangitis (AC) has specific features that constitute an entity other than primary biliary cirrhosis (PBC). We compared clinical, laboratory, and liver biopsy features; response to treatment; and the follow-up of two groups of patients. The first group comprised seven patients with AC criteria-PBC with negative antimitochondrial antibodies (AMAs) and positive antinuclear antibodies (ANAs)-termed the PBC AMA-negative group; the second was made up of another seven PBC patients with positive AMA, labeled the PBC AMA-positive group. We found that the PBC AMA-negative group had, besides negative AMAs and positive ANAs, a significantly higher incidence of asthenia, a higher and earlier incidence of liver failure, and higher ANA titers and serum immunoglobulin G levels than the PBC AMA-positive group. There were no significant differences in the other laboratory tests, although the PBC AMA-negative group showed higher serum bilirubin and aminotransferase and lower serum alkaline phosphatase and immunoglobulin M levels. Liver histological data were similar in both groups. Patients in the PBC AMA-negative group, with more markedly abnormal liver tests, responded to immunosuppressive therapy. We concluded that patients with criteria for PBC but with negative AMAs and positive ANAs have a few specific features that fall between PBC and autoimmune chronic hepatitis. This finding suggests that these patients have a different disease, for which autoimmune cholangitis seems to be an appropriate name.